Osteoporoz genetiği

Kara, Nurten; Alaylı, Gamze; tural, sengul

Osteoporoz genetiği

Şengül TURAL, (Ondokuz Mayıs Üniversitesi, Tıp Fakültesi, Tıbbi Genetik Anabilim Dalı, Samsun, Türkiye)

Nurten KARA, (Ondokuz Mayıs Üniversitesi, Tıp Fakültesi, Tıbbi Genetik Anabilim Dalı, Samsun, Türkiye)

Gamze ALAYLI (Ondokuz Mayıs Üniversitesi, Tıp Fakültesi, Fiziksel Tıp ve Rehabilitasyon Anabilim Dalı, Samsun, Türkiye)

Türk Osteoporoz Dergisi

9 1

Yıl: 2011 Cilt: 17 Sayı: 3 Sayfa Aralığı: 100 - 109 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

Osteoporoz genetiği

Öz:

Osteoporoz, kemik mineral yoğunluğunun azalması ve kemik dokusunun mikro yapısının bozulması ile karakterize multifaktöriyel bir hastalıktır. Kemik mineral yoğunluğunu (KMY) etkileyen bir çok çevresel faktör olmasına rağmen son yıllarda yapılan çalışmalarda genetik yapının osteoporoz patogenezindeki etkisi üzerinde durulmuş ve kemik kütlesi üzerine etkisi olan bir çok aday genin varlığı rapor edilmiştir. Çeşitli ikiz ve aile çalışmaları kemik oluşumunda genetik faktörlerin etkisinin ilişkili kemik parametreleriyle birlikte %50-80 olduğunu göstermektedir. Kemik kütlesini etkileyen birçok genin varlığı bildirilmiştir. Asosiasyon çalışmaları, aday gen polimorfizmleri, meta-analizler ve daha yeni olan genom çaplı çalışmalar ile KMY ve osteoporoz fenotipiyle ilişkili diğer genler belirlenmiştir. Bu derlemede, osteoporozun tanımlanmasından sonra, osteoporoz genetiği, aday gen yaklaşımları, bağlantı (linkaj) analizleri, QTL (kantitatif karakter lokus)’lar, aile ve ikiz çalışmaları, deney hayvanı çalışmaları, GWAS (Genom çaplı asosiasyon çalışmaları) meta analizler, gen ekspresyon çalışmaları ve farmakogenetik çalışmalar ile açıklanmaya çalışılmıştır. Osteoporozla ilişkili yeni genlerin belirlenmesi osteoporozun tedavisi ve önlenmesinde oldukça yararlı olacaktır. Teknolojik gelişmelerle; genom çaplı dizileme, birçok genom projesi, osteoporozla ilişkili allellerin tanımlanmasına izin verecek ve osteoporozun mimarisi hakkında daha geniş bilgi edinilmesini sağlayacaktır. Gelecekte daha kapsamlı çalışmaların ve fonksiyonel analizlerin yapılması umut edilmektedir. Yapılan ve yapılacak olan kapsamlı çalışmaların sonuçlarının değerlendirilmesi osteoporozun erken tanısında yararlı olacaktır. Bunun yanı sıra elde edilen veriler, beslenme ve ilaç tedavisinde kişisel profillerinin belirlenmesini sağlayarak tedavide de yararlı olacaktır. (Türk Os te opo roz Dergisi 2011;17:100-9)

Anahtar Kelime:

Konular: Genel ve Dahili Tıp

Genetics of osteoporosis

Öz:

Osteoporosis is a multifactorial disease characterized by a decrease bone mineral density (BMD) and micro-architectural deterioration of bone structure. Although there are several environmental influences on BMD, a genetic contribution to the pathogenesis of osteoroposis has recently been recognized. Twin and family studies have demonstrated an importanat genetic component of osteoporosis regarding many parameters of bone properties with a heredity of 50-80%. The existence of many candidate genes which have effect on bone mass was reported. Association studies based on candidate gene polymorphisms and subsequent meta-analyses, and the more recent genome-wide association studies (GWAS), have clearly identified a handful of genes associated with BMD and other osteoporosis related phenotypes. In this rewiev, after definition osteoporosis, hertitability of osteoporosis was explained by candidate gene approach, linkaj analysis, QTL (Quantitative Trait Loci)’s, family-based and twin studies, animal studies, GWAS meta analysis, gene expression studies and pharmacogenetics. Identifying osteoporosis related genes may provide new routes for therapeutic intervention and osteoporosis prevention. Technological developments, such as genome-wide sequencing and the thousand genome project, will permit identification of these alleles and give a more complete picture of the genetic architecture of osteoporosis. Also further largescale studies and functional analyses can be expected in the future; these will be highly relevant both for he diagnosis of osteoporosis with individual risk profiles, and for nutritional and pharmaceutical treatment. (Turkish Journal of Osteoporosis 2011;17:100-9)

Anahtar Kelime:

Konular: Genel ve Dahili Tıp

Belge Türü: Makale Makale Türü: Derleme Erişim Türü: Erişime Açık

1. Kutsal YG. Osteoporozda Kemik Kalitesi. Kutsal YG, editör. Görüntüleme Yöntemleri’nde. Ankara, Güneş Kitabevi Ltd. Şti. 2004, p.193-212.
2. Kartal B, Başer M. [Women Health Problems That Affect Quality of Life: Review]. Turkiye Klinikleri J Gynecol Obst 2011;21:195-200.
3. Mitchell BD, Yerges-Armstrong LM. The Genetics of Bone Loss: Challenges and Prospects. J Clin Endocrinol Metab 2011;96:1258-68.
4. Gennari L, Becherini L, Falchetti A, Masi L, Massart F, Brandi ML. Genetics of osteoporosis: role of steroid hormone receptor gene polymorphisms. J Steroid Biochem Mol Biol 2002;81:1-24.
5. Vilela P, Nunes T. Osteoporosis. Neuroradiology 2011;53 (Suppl 1):185–9.
6. Caliri A, De Filippis L, Bagnato GL, Bagnato GF. Osteoporotic fractures: mortality and quality of life. Panminerva Med 2007;49:21-7.
7. Obermayer-Pietsch B. Genetics of Osteoporosis. Wien Med Wochenschr 2006;156:162-7.
8. Cvijetic S, Grazio S, Kastelan D, Korsic M. Epidemiology of osteoporosis. Arh Hig Rada Toksikol 2007;58:13-8.
9. Zajickova K, Zofkova I. Osteoporosis: Genetic Analysis of Multifactorial Disease. Endocr Regul 2003;37:31-44.
10. Lee HJ, Kim SY, Kim GS, Hwang JY, Kim YJ, Jeong B, et al. Fracture, bone mineral density, and the effects of calcitonin receptor gene in postmenopausal Koreans. Osteoporos Int 2010;21:1351-60.
11. Peacock M, Turner CH, Econs MJ, Foroud T. Genetics of Osteoporosis. Endocr Rev 2002;23:303-26.
12. Williams FM, Spector TD. The Genetics Of Osteoporosis. Acta Reumatol Port 2007;32:231-40.
13. Gennari L, Merlotti D, De Paola V, Calabrò A, Becherini L, Martini G, et al. Estrogen Receptor Gene Polymorphisms and the Genetics of Osteoporosis: A HuGE Review. Am J Epidemiol 2005;161:307-20.
14. Rizzoli R, Bonjour JP, Ferrari SL. Osteoporosis, genetics and hormones. J Mol Endocrinol 2001;26:79-94.
15. Uitterlinden AG, van Meurs JB, Rivadeneira F, Pols HA. Identifying genetic risk factors for osteoporosis. J Musculoskelet Neuronal Interact 2006;6:16-26.
16. Ferrari S. Human genetics of osteoporosis. Best Pract Res Clin Endocrinol Metab 2008;22:723-35.
17. Wood RJ. The Genetics of Osteoporosis: Vitamin D Receptor Polymorphisms. Annu Rev Nutr 1998;18:233-58.
18. Sarıdoğan ME. Osteoporoz Epidemiyolojisi. Modern Tıp Seminerleri: Osteoporoz, Kutsal YG, editör. 2. Baskı. Ankara: Güneş Kitabevi Ltd. Şti.; 2001. p. 6-21.
19. Tanakol R. Fizyopatolojik etmenler. Kutsal YG, editör. Osteoporozda Kemik Kalitesi’nde. 1. baskı Ankara: Güneş Kitabevi Ltd. Şti.; 2004. p. 3-70.
20. Garcia-Closas M, Hankinson SE, Ho S, Malins DC, Polissar NL, Schaefer SN, et al. Factors critical to the design and execution of epidemiologic studies and description of an innovative technology to follow the progression from normsl to tumor tissue. J Natl Cancer Inst Monogr 2000;(27):147-56.
21. Passarge E. Renkli Genetik Atlası, Formal Genetik: Polimorfizm. Luleci G, Sakizli M. 2.baskı,İstanbul: Nobel Tıp - Yüce Yayınları; 2000. p.156.
22. Carey J, White B. Medical Genetics. Third Edition. Missouri: Mosby; 2006. p.29.
23. Nussbaum RL, McInnes RR, Willard HF. Genetics in medicine. Sixth Edition Philadephia: Saunders Elsevier; 2004. p.87.
24. Ollier WE. Cytokine genesanddisease susceptibility. Cytokine 2004;28:174-8.
25. Zheng HF, Spector TD, Richards JB. Insights into the genetics of osteoporosis from recent genome-wide association studies. Expert Rev Mol Med 2011;13:e28.
26. Stein GS, Lian JB, van Wijnen AJ, Stein JL. The osteocalcin gene: a model for multiple parameters of skeletal-specific transcriptional control. Mol Biol Rep 1997;24:185-96.
27. Durmaz B. Biyokimyasal Göstergeler. Kutsal YG, editör. Osteoporozda Kemik Kalitesi’nde. 8. Baskı Ankara, Güneş Kitabevi Ltd. Şti.; 2004. p. 175-189.
28. Chen HY, Tsai HD, Chen WC, Wu JY, Tsai FJ, Tsai CH. Relation of Polimorphism in the Promotor Region for the Human Osteocalcin Gene to Bone Mineral Density Occurrence of Osteoporosis in Postmeopausal Chinese Women in Taiwan. J Clin Lab Anal 2001;15:251-5.
29. Dohi Y, Iki M, Ohgushi H, Gojo S, Tabata S, Kajita E, et al. A novel polymorphism in the promoter region for human osteocalcin gene: the possibility of acorrelation with bone mineral density in postmenopausal Japanese women. J Bone Miner Res 1998;13:1633-9.
30 .Erdogan MO, Yıldız H, Artan S, Solak M, Taşcıoğlu F, Dündar U, et al. Association of estrogen receptor alpha and collagen type I alpha 1 gene polymorphisms with bone mineral density in postmenopausal women. Osteoporos Int 2011;22:1219-25.
31. Mann V, Hobson EE, Li B, Stewart TL, Grant SFA, Robins SP, Aspden RM, Ralston SH. A COL1A1Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Invest 2001; 107, 899-907.
32. Simsek M, Cetin Z, Bilgen T, Taskin O, Luleci G, Keser I. Effects of hormone replacement therapy on bone mineral density in Turkish patients with or without COL1A1 Sp1 binding site polymorphism. J Obstet Gynaecol Res 2008;34:73-7.
33. Garcia-Giralt N, Nogués X, Enjuanes A, Puig J, Mellibovsky L, Bay- Jensen A, et al. Two new single nucleotide polymorphisms in the COLIA1upstream regulatory region and their relationship with bone mineral density. J Bone Miner Res 2002;17:384-93.
34. Blades HZ, Arundel P, Carlino WA, Dalton A, Crook JS, Freeman JV, et al. Collagen gene polymorphisms influence fracture risk and bone mass acquisition during childhood and adolescent growth. Bone 2010;47:989-94.
35. Safarova A, Pala HG, Erbil D, Gezer NS. [Bone Mineral Density and Endogen Sex Steroid Hormone Association in Postmenopausal Healthy Women]. Journal of Turkish Society of Obstetrics and Gynecology, (J Turk Soc Obstet Gynecol) 2011;8:118-24.
36. Li X, Huang J, Yi P, Bambara RA, Hilf R, Muyan M. Single-chain estrogen receptors (ERs) reveal that the ERalpha/beta heterodimer emulates functions of the ERalpha dimer in genomic estrogen signaling pathways. Mol Cell Biol 2004;24:7681-94.
37. Jeedigunta Y, Bhoomi Reddy PR, Kolla VK, Munshi A, Ananthapur V, Narasimulu G, et al. Association of estrogen receptor α gene polymorphisms with BMD and their affecton estradiol levels in preand postmenopausal women in south Indian population from Andhra Pradesh. Clin Chim Acta 2010;411:597-600.
38. Pollak A, Rokach A, Blumenfeld A, Rosen LJ, Resnik L, Dresner Pollak R. Association of oestrogen receptor alpha gene polymorphism with the angiographic extent of coronary artery disease. Eur Heart J 2004;25:240-5.
39. Bandrés E, Pombo I, González-Huarriz M, Rebollo A, López G, García- Foncillas J. Association between bone mineral density and polymorphism of the VDR, ERalpha, COL1A1 and CTR genes in Spanish postmenopausal women. J Endocrinol Invest 2005;28:312-21.
40. Currò M, Marini H, Alibrandi A, Ferlazzo N, Condello S, Polito F, et al. The ESR2 AluI gene polymorphism is associated with bone mineral density in postmenopausal women. J Steroid Biochem Mol Biol 2011;127:413-7.
41. Ralston SH. Genetics of osteoporosis. Ann N Y Acad Sci 2010;1192:181-9.
42. Wolfe LA 3rd, Fling ME, Xue Z, Armour S, Kerner SA, Way J, et al. In vitro characterization of a human calcitonin receptor gene polymorphism. Mutat Res 2003;522:93-105.
43. Lau RY, Guo X. A Review on Current Osteoporosis Research:With Special Focus on Disuse Bone Loss. J Osteoporos 2011;2011:293808.
44. Kurban S, Mehmetoğlı I. Osteoprotegerin, Rank ve Rank Ligandı. Türk Biyokimya Dergisi (Turkish Journal of Biochemistry–Turk J Biochem) 2007;32:178–84.
45. Roshandel D, Holliday KL , Pye SR, Boonen S, Borghs H, Vanderschueren D. Genetic Variation in the RANKL/RANK/OPG Signaling Pathway Is Associated With Bone Turnover and Bone Mineral Density in Men. Journal of Bone and Mineral Research 2010; 25(8),1830–1838.
46. Roshandel D, Holliday KL, Pye SR, Boonen S, Borghs H, Vanderschueren D, et al. Genetic variation in the RANKL/RANK/OPG signaling pathway is associated with bone turnover and bone mineral density in men. J Bone Miner Res 2010;25:1830-8.
47. Ferrari SL, Rizzoli R. Gene variants for osteoporosis and their pleiotropic effects in aging. Mol Aspects Med 2005;26:145-67.
48. Stewart TL, Ralston SH. Role of genetic factors in the pathogenesis of osteoporosis. J Endocrinol 2000;166:235-45.
49. Gong Y, Vikkula M, Boon L, Liu J, Beighton P, Ramesar R, et al. Osteoporosis-pseudoglioma syndrome, adisorder affecting skeletal strength and vision, is assgnerd to chromosome region 11q12-13. Am J Hum Genet 1996;59:146-51.
50. Deng HW, Xu FH, Conway T, Deng XT, Li JL, Davies KM, et al. Is population bone mineral density variation linked to the marker D11S987 on chromosome 11q12-13? J Clin Endocrinol Metab 2001;86:3735-41.
51. Ralston SH. Genetics of Osteoporosis. Proceedings of the Nutrition Society 2007;66:158–65.
52. Duncan EL, Danoy P, Kemp JP, Leo PJ, McCloskey E, Nicholson GC, et al. Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk. PLoS Genet 2011;7:e1001372.
53. Kou I, Takahashi A, Urano T, Fukui N, Ito H, Ozaki K, et al. Common variants in a novel gene, FONG on chromosome 2q33.1 confer risk of osteoporosis in Japanese. PLoS One 2011;6:e19641.
54. Logar DB, Komadina R, Prezelj J, Ostanek B, Trost Z, Marc J. Expression of bone resorption genes in osteoarthritis and in osteoporosis. J Bone Miner Metab 2007;25:219-25.
55. Marini F, Brandi ML. Pharmacogenetics of osteoporosis. F1000 Biol Rep 2010;2:63.
56. Kruk M, Ralston SH, Albagha OM. LPR polymorphisms and response to risedronate treatment in osteoporotic men. Calcif Tissue Int 2009;84:171-9.
57. Choi HJ, Choi JY, Cho SW, Kang D, Han KO, Kim SW, et al. Genetic polymorphism of geranyıgeranyl diphosphate synthase (GGSPI) predicts bone density response to bisphosphonate theraphy in Korean women. Yonsei Med J 2010;51:231-8.
58. Fu X, Zhao X, Lu H, Jiang F, Ma X, Zhu S. Association between sleep duration and bone mineral density in Chinese women. Bone 2011;49:1062-6.
59. Greco EA, Fornari R, Rossi F, Santiemma V, Prossomariti G, Annoscia C, et al. Introduction Is obesity protective for osteoporosis? Evaluation of bone mineral density in individuals with high body mass index. Int J Clin Pract 2010;64:817-20.
60. Maurel DB, Boisseau N, Benhamou CL, Jaffre C. Alcohol and bone: review of dose effects and mechanisms .Osteoporos Int 2012;23:1-16.
61. Kraemer B, Schneider S, Rothmund R, Fehm T, Wallwiener D, Solomayer EF. Influence of pregnancy on bone density: a risk factor for osteoporosis? Measurements of the calcaneus by ultrasonometry. Arch Gynecol Obstet 2011;14.

APA	tural s, Kara N, Alaylı G (2011). Osteoporoz genetiği. , 100 - 109.
Chicago	tural sengul,Kara Nurten,Alaylı Gamze Osteoporoz genetiği. (2011): 100 - 109.
MLA	tural sengul,Kara Nurten,Alaylı Gamze Osteoporoz genetiği. , 2011, ss.100 - 109.
AMA	tural s,Kara N,Alaylı G Osteoporoz genetiği. . 2011; 100 - 109.
Vancouver	tural s,Kara N,Alaylı G Osteoporoz genetiği. . 2011; 100 - 109.
IEEE	tural s,Kara N,Alaylı G "Osteoporoz genetiği." , ss.100 - 109, 2011.
ISNAD	tural, sengul vd. "Osteoporoz genetiği". (2011), 100-109.

APA	tural s, Kara N, Alaylı G (2011). Osteoporoz genetiği. Türk Osteoporoz Dergisi, 17(3), 100 - 109.
Chicago	tural sengul,Kara Nurten,Alaylı Gamze Osteoporoz genetiği. Türk Osteoporoz Dergisi 17, no.3 (2011): 100 - 109.
MLA	tural sengul,Kara Nurten,Alaylı Gamze Osteoporoz genetiği. Türk Osteoporoz Dergisi, vol.17, no.3, 2011, ss.100 - 109.
AMA	tural s,Kara N,Alaylı G Osteoporoz genetiği. Türk Osteoporoz Dergisi. 2011; 17(3): 100 - 109.
Vancouver	tural s,Kara N,Alaylı G Osteoporoz genetiği. Türk Osteoporoz Dergisi. 2011; 17(3): 100 - 109.
IEEE	tural s,Kara N,Alaylı G "Osteoporoz genetiği." Türk Osteoporoz Dergisi, 17, ss.100 - 109, 2011.
ISNAD	tural, sengul vd. "Osteoporoz genetiği". Türk Osteoporoz Dergisi 17/3 (2011), 100-109.